Wearable Technologies Using Peripheral Neuromodulation to Enhance Mobility and Gait Function in Older Adults-A Narrative Review.

BACKGROUND: Mounting evidence suggests that wearable technologies using peripheral neuromodulation can provide novel ways of improving mobility and gait function in various patient populations including older adults. The purpose of this narrative review is to provide an overview of wearable technologies/devices to improve mobility and gait function through noninvasive peripheral neuromodulation in older adults over the age of 65 and to indicate the suggested mechanism of action behind these technologies. METHODS: We performed searches for articles and conference abstracts written in English, using the following databases: Embase Classic+Embase from 1947 to July 15, 2021; Ovid MEDLINE; Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions from 1946 to July 15, 2021; PubMed; and Scopus. RESULTS: Forty-one technologies met the inclusion/exclusion criteria. We found that the primary implementation of the 41 technologies can be divided into 3 main categories: sensory substitution, sensory augmentation (open loop, closed loop), and motor stimulation. Using these technologies, various aspects of mobility are treated or addressed, including, gait function, fall risk, foot drop, navigating environment, and postural control. CONCLUSIONS: This narrative review summarizes wearable technologies that are currently commercially available and in stages of research and development. Overall, studies suggest that wearable peripheral neuromodulation technologies can improve aspects of mobility for older adults. Existing literature suggests that these technologies may lead to physiological changes in the brain through sensory reweighting or other neuroplastic mechanisms to enhance the performance of mobility and gait function in older adults over the age of 65.

Brain activity during dual-task standing in older adults.

BACKGROUND: In older adults, the extent to which performing a cognitive task when standing diminishes postural control is predictive of future falls and cognitive decline. The neurophysiology of such "dual-tasking" and its effect on postural control (i.e., dual-task cost) in older adults are poorly understood. The purpose of this study was to use electroencephalography (EEG) to examine the effects of dual-tasking when standing on brain activity in older adults. We hypothesized that compared to single-task "quiet" standing, dual-task standing would decrease alpha power, which has been linked to decreased motor inhibition, as well as increase the ratio of theta to beta power, which has been linked to increased attentional control. METHODS: Thirty older adults without overt disease completed four separate visits. Postural sway together with EEG (32-channels) were recorded during trials of standing with and without a concurrent verbalized serial subtraction dual-task. Postural control was measured by average sway area, velocity, and path length. EEG metrics included absolute alpha-, theta-, and beta-band powers as well as theta/beta power ratio, within six demarcated regions-of-interest: the left and right anterior, central, and posterior regions of the brain. RESULTS: Most EEG metrics demonstrated moderate-to-high between-day test-retest reliability (intra-class correlation coefficients > 0.70). Compared with quiet standing, dual-tasking decreased alpha-band power particularly in the central regions bilaterally (p = 0.002) and increased theta/beta power ratio in the anterior regions bilaterally (p < 0.001). A greater increase in theta/beta ratio from quiet standing to dual-tasking in numerous demarcated brain regions correlated with greater dual-task cost (i.e., absolute increase, indicative of worse performance) to postural sway metrics (r = 0.45-0.56, p < 0.01). Lastly, participants who exhibited greater alpha power during dual-tasking in the anterior-right (r = 0.52, p < 0.01) and central-right (r = 0.48, p < 0.01) regions had greater postural sway velocity during dual-tasking. CONCLUSION: In healthy older adults, alpha power and theta/beta power ratio change with dual-task standing. The change in theta/beta power ratio in particular may be related to the ability to regulate standing postural control when simultaneously performing unrelated, attention-demanding cognitive tasks. Modulation of brain oscillatory activity might therefore be a novel target to minimize dual-task cost in older adults.

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study.

The pupillary response reflects mental effort (or cognitive workload) during cognitive and/or motor tasks including standing postural control. EEG has been shown to be a non-invasive measure to assess the cortical involvement of postural control. The purpose of this study was to understand the effect of increasing postural task difficulty on the pupillary response and EEG outcomes and their relationship in young adults. Fifteen adults completed multiple trials of standing: eyes open, eyes open while performing a dual-task (auditory two-back), eyes occluded, and eyes occluded with a dual-task. Participants stood on a force plate and wore an eye tracker and 256-channel EEG cap during the conditions. The power spectrum was analyzed for absolute theta (4−7 Hz), alpha (8−13 Hz), and beta (13−30 Hz) frequency bands. Increased postural task difficulty was associated with greater pupillary response (p < 0.001) and increased posterior region alpha power (p = 0.001) and fronto-central region theta/beta power ratio (p = 0.01). Greater pupillary response correlated with lower posterior EEG alpha power during eyes-occluded standing with (r = −0.67, p = 0.01) and without (r = −0.69, p = 0.01) dual-task. A greater pupillary response was associated with lower CoP displacement in the anterior−posterior direction during dual-task eyes-occluded standing (r = −0.60, p = 0.04). The pupillary response and EEG alpha power appear to capture similar cortical processes that are increasingly utilized during progressively more challenging postural task conditions. As the pupillary response also correlated with task performance, this measurement may serve as a valuable stand-alone or adjunct tool to understand the underlying neurophysiological mechanisms of postural control.

Pupillary Response to Postural Demand in Parkinson's Disease.

Background: Individuals with Parkinson's disease (PD) may need to spend more mental and physical effort (i.e., cognitive workload) to maintain postural control. Pupillary response reflects cognitive workload during postural control tasks in healthy controls but has not been investigated as a measure of postural demand in PD. Objectives: To compare pupillary response during increased postural demand using vision occlusion and dual tasking between individuals with PD and healthy controls. Methods: Thirty-three individuals with PD and thirty-five healthy controls were recruited. The four conditions lasted 60 s and involved single balance task with eyes open; single balance task with eyes occluded; dual task with eyes open; dual task with eyes occluded. The dual task comprised the Auditory Stroop test. Pupillary response was recorded using an eye tracker. The balance was assessed by using a force plate. Two-way Repeated Measures ANOVA and LSD post-hoc tests were employed to compare pupillary response and Center of Pressure (CoP) displacement across the four conditions and between individuals with PD and healthy controls. Results: Pupillary response was higher in individuals with PD compared to healthy controls (p = 0.009) and increased with more challenging postural conditions in both groups (p < 0.001). The post-hoc analysis demonstrated increased pupillary response in the single balance eyes occluded (p < 0.001), dual task eyes open (p = 0.01), and dual task eyes occluded (p < 0.001) conditions compared to single task eyes open condition. Conclusion: Overall, the PD group had increased pupillary response with increased postural demand compared to the healthy controls. In the future, pupillary response can be a potential tool to understand the neurophysiological underpinnings of falls risk in the PD population.

Exercise interventions for older adults with Alzheimer's disease: a systematic review and meta-analysis protocol.

BACKGROUND: The growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. METHODS: This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. DISCUSSION: This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175016 .

Cognitive workload during verbal abstract reasoning in Parkinson's disease: a pilot study.

BACKGROUND: Pupillary response reflects cognitive workload during processing speed, working memory, and arithmetic tasks in Parkinson's disease (PD). Abstract reasoning, a higher-order cognitive function that relates different objects, events, or thoughts in a similar manner, may also be compromised in PD. The aim of this study was to compare pupillary response as a measure of cognitive workload while completing a verbal abstract reasoning test between patients with PD and age-matched controls. METHODS: Nineteen non-demented individuals with PD (66.6 ± 8.9 years) and 10 healthy controls (65.3 ± 7.3 years) were recruited. A remote eye tracker recorded the pupillary response at 60 Hz, while the participants were performing the Similarities test of Wechsler Adult Intelligence Scale-IV. Outcome measures included pupillary response, evaluated by the Index of Cognitive Activity (ICA), and behavioral responses of the Similarities test. RESULTS: The PD group (scaled scores = 8.9 ± 2.2) did not show impairment in behavioral performance on Similarities test compared with healthy controls (scaled scores = 8.8 ± 2.3; p = .91). However, the PD group (ICA = .32 ± .09) demonstrated significantly greater cognitive workload during the Similarities test compared to controls (ICA = .24 ± .08; p = .03). CONCLUSIONS: Non-demented individuals with PD exerted greater cognitive workload to complete a verbal abstract reasoning task despite similar behavioral performance compared to healthy controls. Clinical utilities of pupillary response to detect and monitor early impairment in higher-order executive function will be the subject of further study in the PD population.

Reliability and Validity of Pupillary Response During Dual-Task Balance in Parkinson Disease.

OBJECTIVE: To investigate the reliability and validity of pupillary response during dual-task balance conditions in individuals with Parkinson disease (PD). DESIGN: Cross-sectional study. SETTING: University of Kansas Medical Center Parkinson's Disease and Movement Disorder Center. PARTICIPANTS: Participants (N=68) included individuals with PD (n=33) and healthy controls (n=35). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pupillary response was the main outcome measure that was measured during the following conditions: single-task balance eyes open, single-task balance eyes occluded, dual-task eyes open, and dual-task eyes occluded. After each condition, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) was administered to assess self-reported cognitive workload. To examine the test-retest reliability of the pupillary response, the conditions were administered twice for each individual within 2 hours. Intraclass correlation coefficients (ICC) were used to analyze the test-retest reliability of pupillary response in each condition for both groups. Pearson's r correlation was used to assess the convergent validity of pupillary response against the NASA-TLX. RESULTS: The test-retest reliability was excellent for both groups in almost all conditions (ICC>0.75). There were no correlations between pupillary response and the NASA-TLX. However, increased mental demand (a subitem of the NASA-TLX) significantly correlated with increased pupillary response in individuals with PD (r=0.38; P=.03). CONCLUSIONS: Pupillary response showed excellent test-retest reliability and validity during dual-task balance for individuals with PD and healthy controls. Overall, these results suggest that pupillary response represents a stable index of cognitive workload during dual-task balance in individuals with PD.

Brain activity during dual task gait and balance in aging and age-related neurodegenerative conditions: A systematic review.

The aims of this systematic review were to investigate (1) real-time brain activity during DT gait and balance, (2) whether changes in brain activity correlate with changes in behavioral outcomes in older adults and people with age-related neurodegenerative conditions. PubMed, PsycINFO, and Web of Science were searched from 2009 to 2019 using the keywords dual task, brain activity, gait, balance, aging, neurodegeneration, and other related search terms. A total of 15 articles were included in this review. Functional near-infrared spectroscopy and electroencephalogram measures demonstrated that older adults had higher brain activity, particularly in the prefrontal cortex (PFC), compared to young adults during dual task gait and balance. Similar neurophysiological results were observed in people with age-related neurodegenerative conditions. Few studies demonstrated a relationship between increased brain activity and better behavioral outcomes. This systematic review supports the notion that aging and age-related neurodegenerative conditions are associated with neuronal network changes, resulting in increased brain activity specifically in the PFC. Further studies are warranted to assess the relationship between increased PFC activation during dual task gait and balance and behavioral outcomes to better optimize the rehabilitation interventions.

Pupillary response: cognitive effort for breast cancer survivors.

PURPOSE: The purpose of this cross-sectional comparative pilot study was to evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer survivors (BCS) with complaints of cognitive dysfunction following chemotherapy. STUDY AIMS: Compare the cognitive effort employed by BCS to healthy controls (HC) during neuropsychological tests (NPT) for memory, sustained attention, verbal fluency, visuospatial ability, processing speed and executive function; and Investigate the relationship between PR-indexed cognitive effort and participants' self-report of cognitive function. METHODS: Self-report of cognitive function was collected from 23 BCS and 23 HC. PR was measured during NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to compare group scores. Between-group effect size (Cohen's d) was calculated for each outcome. Correlation between mean self-report scores and PR values, as well as 95% confidence intervals, was calculated. RESULTS: No group differences were demonstrated for NPT performance. BCS reported more issues with cognitive function than HC (p < .0001). A group effect for BCS was seen with PR-indexed cognitive effort for components of most NPT (p < .05). PR was correlated with most self-report measures of cognitive function (r = 0.33-0.45). CONCLUSIONS: PR sensitivity to cognitive effort across a variety of NPT and correlation with self-report of cognitive function was demonstrated. The portability, affordability, and "real-time" aspects of PR are attractive for potential use in the clinic setting to assess cognitive function. A larger study is needed to confirm these results. Prospective investigation of PR in BCS is needed to demonstrate sensitivity to cognitive function changes over time.

Increased Postural Demand Is Associated With Greater Cognitive Workload in Healthy Young Adults: A Pupillometry Study.

Introduction: Balance tasks require cognitive resources to ensure postural stability. Pupillometry has been used to quantify cognitive workload of various cognitive tasks, but has not been studied in postural control. The current investigation utilized pupillometry to quantify the cognitive workload of postural control in healthy young adults. We hypothesized that cognitive workload, indexed by pupil size, will increase with challenging postural control conditions including visual occlusion and cognitive dual tasking. Methods: Twenty-one young healthy adults (mean ± standard error of the mean), (age = 23.2 ± 0.49 years; 12 females) were recruited for this study. Participants completed four tasks: (1) standing with eyes open; (2) standing with eyes occluded (3) standing with eyes open while performing an auditory Stroop task; and (4) standing with eyes occluded while performing an auditory Stroop task. Participants wore eye tracking glasses while standing on a force platform. The eye tracking glasses recorded changes in pupil size that in turn were converted into the Index of Cognitive Activity (ICA). ICA values were averaged for each eye and condition. A two-way Analysis of Variance with post-hoc Sidak correction for pairwise comparisons was run to examine the effect of visual occlusion and dual tasking on ICA values as well on Center of Pressure (CoP) sway velocity in anterior-posterior (AP) and medio-lateral (ML) directions. A Pearson's correlation coefficient was utilized to determine the relationship between ICA values and CoP sway velocity. Results: Significant within-condition effect was observed with visual occlusion for the right eye ICA values (p = 0.008). Right eye ICA increased from eyes open to eyes occluded conditions (p = 0.008). In addition, a significant inverse correlation was observed between right eye ICA values and CoP sway velocity in the ML direction across all the conditions (r = -0.25, p = 0.02). Conclusion: This study demonstrated support for increased cognitive workload, measured by pupillometry, as a result of changes in postural control in healthy young adults. Further research is warranted to investigate the clinical application of pupillometry in balance assessment.

Pupillary Response to Cognitive Demand in Parkinson's Disease: A Pilot Study.

Previous studies have shown that pupillary response, a physiological measure of cognitive workload, reflects cognitive demand in healthy younger and older adults. However, the relationship between cognitive workload and cognitive demand in Parkinson's disease (PD) remains unclear. The aim of this pilot study was to examine the pupillary response to cognitive demand in a letter-number sequencing (LNS) task between 16 non-demented individuals with PD (age, median (Q1-Q3): 68 (62-72); 10 males) and 10 control participants (age: 63 (59-67); 2 males), matched for age, education, and Montreal Cognitive Assessment (MOCA) scores. A mixed model analysis was employed to investigate cognitive workload changes as a result of incremental cognitive demand for both groups. As expected, no differences were found in cognitive scores on the LNS between groups. Cognitive workload, exemplified by greater pupil dilation, increased with incremental cognitive demand in both groups (p = 0.003). No significant between-group (p = 0.23) or interaction effects were found (p = 0.45). In addition, individuals who achieved to complete the task at higher letter-number (LN) load responded differently to increased cognitive demand compared with those who completed at lower LN load (p < 0.001), regardless of disease status. Overall, the findings indicated that pupillary response reflects incremental cognitive demand in non-demented people with PD and healthy controls. Further research is needed to investigate the pupillary response to incremental cognitive demand of PD patients with dementia compared to non-demented PD and healthy controls. Highlights -Pupillary response reflects cognitive demand in both non-demented people with PD and healthy controls-Although not significant due to insufficient power, non-demented individuals with PD had increased cognitive workload compared to the healthy controls throughout the testing-Pupillary response may be a valid measure of cognitive demand in non-demented individuals with PD-In future, pupillary response might be used to detect cognitive impairment in individuals with PD.

Individuals with mild MS with poor sleep quality have impaired visuospatial memory and lower perceived functional abilities.

BACKGROUND: Sleep disturbances are common in individuals with Multiple Sclerosis (MS), but the impact of poor sleep quality on cognitive and physical function in individuals with MS is less clear. OBJECTIVE/HYPOTHESIS: The purpose of this study was to examine the relationship between sleep quality and cognitive and physical function in individuals with mild MS. METHODS: Forty individuals with relapsing-remitting or secondary-progressive MS (50.3 ± 11.6 years of age) participated. The Pittsburgh Sleep Quality Index (PSQI) was used to index sleep quality. A PSQI of ≤5 was considered good sleep quality and >5 was considered poor sleep quality. Cognitive function was assessed using a battery of cognitive tests, and physical function was assessed using 2 objective measures and a self-report measure. RESULTS: Thirteen individuals (32.5%) indicated good sleep quality and 27 (67.5%) of the participants reported poor sleep quality. Those with good sleep quality performed significantly better on a visuospatial memory test (p = 0.025) and reported higher functional abilities (p < 0.001) compared to those with poor sleep quality. There was no difference in performance on the cognitive tests of verbal memory, information processing, or executive function, or the objective function measures. Individuals with poor sleep quality had higher levels of fatigue, depression, and anxiety, and lower quality of life. CONCLUSIONS: Visuospatial memory appears to be the memory domain particularly associated with poor sleep quality in people with mild MS. Also, individuals with mild MS with poor sleep quality may underestimate their functional abilities.

The Relationship Between Apolipoprotein ε4 Carrier Status and Sleep Characteristics in Cognitively Normal Older Adults.

The apolipoprotein (APOE) ε4 allele, a well-described genetic risk factor for late-onset Alzheimer disease (AD), is associated with sleep disturbances even in cognitively normal older adults, although it is not clear whether this association is independent of sleep apnea. We sought to extend previous studies by examining whether cognitively normal older adults without self-reported sleep apnea who carry the APOE ε4 allele have altered sleep characteristics compared to noncarriers. Data from N = 36 (APOE ε4 carriers [n = 9], noncarriers [n = 27]) cognitively normal older adults (Clinical Dementia Rating [CDR] scale = 0) without self-reported sleep apnea were used for these analyses. Participants wore an actigraph for 7 days to determine sleep characteristics. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to assess sleep quality and daytime sleepiness, respectively. The APOE ε4 carriers had a higher number of awakenings compared to the noncarriers ( P = .02). There was no significant difference in the PSQI global score and the ESS; however, the PSQI subcomponent of daily disturbances was significantly higher in APOE ε4 carriers ( P = .03), indicating increased daytime dysfunction is related to disrupted sleep. This study provides evidence that individuals who are cognitively normal and genetically at risk of AD may have disrupted sleep. These findings are consistent with prior studies and suggest that sleep disruption may be present in the presymptomatic stages of AD.

Randomized controlled trial of exercise interventions to improve sleep quality and daytime sleepiness in individuals with multiple sclerosis: A pilot study.

BACKGROUND: Nearly 70% of individuals with multiple sclerosis (MS) experience sleep disturbances. Increasing physical activity in people with MS has been shown to produce a moderate improvement in sleep quality, and exercise has been shown to improve sleep quality in non-neurologically impaired adults. OBJECTIVE: The purpose of this pilot randomized controlled trial study was to examine the effect of two exercise interventions on sleep quality and daytime sleepiness in individuals with MS. METHODS: Twenty-eight individuals with relapsing-remitting or secondary progressive MS were randomized into one of two 12-week exercise interventions: a supervised, moderate-intensity aerobic exercise (AE) program or an unsupervised, low-intensity walking and stretching (WS) program. Only individuals who were ≥ 70% compliant with the programs were included in analysis (n = 12 AE; n = 10 WS). RESULTS: Both groups demonstrated a moderate improvement in sleep quality, although only the improvement by the WS group was statistically significant. Only the AE group demonstrated a significant improvement in daytime sleepiness. Change in sleep quality and daytime sleepiness was not correlated with disease severity or with change in cardiovascular fitness, depression, or fatigue. CONCLUSION: The mechanisms for improvement in sleep quality and daytime sleepiness need further investigation, but may be due to introduction of zeitgebers to improve circadian rhythm.